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Active, not recruitingNCT02814591Updated Nov 23, 2022

Development of a Non-invasive Assessment of Human Bone Quality Using Spatially Offset Raman Spectroscopy

An observational study in Osteoarthritis, Osteoporosis and Osteogenesis Imperfecta, sponsored by University College, London. Active, not recruiting. Open to participants aged 0 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-11-23.

Sponsored by University College, London · Observational

Study type
Observational
Model
Cohort
Time perspective
Other
Enrollment
245
Ages
0 Years and older
Sex
All
01

Study summary

In this study spatially offset Raman spectroscopy (SORS), which allows the collection of Raman spectra through turbid media, is being applied to collect Raman spectra of bone. The principal aim to find ways to use Raman spectroscopy to assess bone quality in vivo.

02

Conditions studied

  • Osteoarthritis
  • Osteoporosis
  • Osteogenesis Imperfecta
  • Rickets / Osteomalacia
  • Bone Infection
03

Who can participate

Ages eligible
0 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Control patients, patients with osteoarthritis, patients with osteoporosis, patients with osteogenesis imperfecta, patients with rickets or osteomalacia, patients with suspected bone infection.

Eligibility criteria

INCLUSION CRITERIA

Cohort 1: 40 volunteers, free from bone disease:

  • Participants must be free from bone disease and not have a family history of OI;
  • Participants to be age and sex matched with OP participants may be recruited among individuals attending the RNOH Metabolic Unit for DXA scanning, who are shown to have normal bone density T score> -2.5;
  • No history of non-accidental fracture;
  • No history of OA or clinical manifestations of disease;
  • No clinical features of OI;
  • Controls will be sex and age matched (within five years) to the disease cohort patients.
  • Children and adults both required

Cohort 2: 40 patients with OI:

  • Patients must have been clinically diagnosed with OI;
  • Where possible participants will be identified from the Royal National Orthopaedic Hospital, Metabolic Unit database; if not from RNOH then diagnosis will be otherwise confirmed

Cohort 3: 40 patients with OA:

  • Patients must have been clinically diagnosed with OA;
  • Participants will be identified from the Royal National Orthopaedic Hospital, Metabolic Unit database; if not from RNOH then diagnosis will be otherwise confirmed

Cohort 4: 40 patients with OI, receiving treatment with bisphosphonates:

  • Patients must have been clinically diagnosed with OI and bisphosphonates prescribed as a course of treatment;
  • 20 Adults and 20 children
  • Where possible participants will be identified from the Royal National Orthopaedic Hospital, Metabolic Unit database; if not from RNOH then diagnosis will be otherwise confirmed
  • Where possible measurements will be acquired prior to the start of treatment and then for up to 4 follow up visits at flexible time points to allow scheduling to coincide with hospital appointments. The minimum time between visits should be 2 months.

Cohort 5: 2x 30 patients with OP (two treatment groups):

  • Patients must have been clinically diagnosed with OP;
  • The first cohort will have been prescribed with bisphosphonate anti-resorptive treatment; the second with anabolic agents. Where treatment has ceased but remains active (long-acting), potential participants may be included at Dr. Keen's discretion.
  • Where possible participants will be identified from the Royal National Orthopaedic Hospital, Metabolic Unit database; if not from RNOH then diagnosis will be otherwise confirmed
  • BMD confirmed with DXA
  • Where possible measurements will be acquired prior to the start of treatment and then up to 4 follow up visits at flexible time points to allow scheduling to coincide with hospital appointments. Minimum time between visits should be 2 months.

Cohort 6: 10-15 participants with rickets, 10-15 participants with osteomalacia

  • Patients must have been clinically diagnosed with rickets/osteomalacia;
  • Blood tests for 25-hydroxyvitamin D should be ≤25 nmol/L
  • Once participants are on treatment a further measurement will be made 6 months afterwards
  • Participants for rickets and osteomalacia groups will be recruited to give a total of 10 complete sets of data per group

Cohort 7: 5 participants with a suspected bone infection

  • Participants will have been diagnosed at RNOH with a suspected bone infection
  • Participants will be scanned around the localised area of suspected infection. Measurements may also be taken away from the infection on the same side and the contralateral anatomical location e.g., if infection is suspected at the right knee then we may also scan further down the right leg and the left leg.
  • Participants may have 1 or 2 visits; the latter to take place after all infection has cleared up. This is not subject to a fixed time frame.

EXCLUSION CRITERIA In general smokers will be excluded. Ex-smokers will be included only if they gave up smoking a minimum of 5 years ago.

Cohort 1: 40 volunteers, free from bone disease:

  • A participant with a history of bone disease or non-accidental fracture
  • Clinical features of bone disease

Cohort 2: 40 patients with OI; Cohort 3: 40 patients with OA; Cohort 6: 20 patients with rickets/osteomalacia • Patients with more than 1 type of bone disease

Cohorts 4, 5 and 6: receiving treatment

  • Patients who have been advised to stop treatment. If the treatment is a long-acting one (i.e., will remain effective in the body) then the participant may be included.
04

Study design

Observational model
Cohort
Time perspective
Other
Enrollment
245 participants (estimated)
Target follow-up
1 Year
Patient registry
Yes

Groups and cohorts

  • Cohort 1: Controls

    40 volunteers free from bone disease. No family histroy of osteogenesis imperfecta (OI). No history of non-accidental fracture. No history of osteoarthritis (OA) or clinical manifestations of disease. No clinical features of OI, OA or osteoporosis (OP). Normal haemoatology and biochemical blood screen. Controls will be gender and age matched (within five years) to the disease cohort patients. Children and adults both required.

    Device: spatially offset Raman spectrometer (SORS)

  • Cohort 2: Patients with ostegenesis imperfecta (OI).

    40 patients with OI. Patients must have been clinically diagnosed with OI. Participants will be identified form the Royal National Orthopaedic Hospital, Metabolic Unit database. Bone mineral density (BMD) confirmed with DXA.

    Device: spatially offset Raman spectrometer (SORS)

  • Cohort 3: Patients with osteoarthritis (OA)

    40 patients with OA. Patients must have been clinically diagnosed with OA. Participants will be identified from the Royal National Orthopaedic Hospital, Metabolic Unit database.

    Device: spatially offset Raman spectrometer (SORS)

  • Cohort 4: Patients with osteoporosis (OI)

    40 patients with OI receiving treatment with bisphosphonates. Patients must have been clinically diagnosed with OI and bisphosphonates prescribed as a course of treatment. 20 Adults and 20 Children. Where possible participants will be identified from the Royal National Orthopaedic Hospital (RNOH), Metabolic Unit Database; if not from the RNOH then diagnosis will be otherwise confirmed.

    Device: spatially offset Raman spectrometer (SORS)

  • Cohort 5: Patients with osteoporosis (OP) (2 treatment groups)

    Patients must have been clinically diagnosed with OP. The first group will have been prescribed with bisphosphonate anti-resorptive treatment; the second with anabolic agents. Where possible participants will be identified from the Royal National Orthopaedic Hospital (RNOH), Metabolic Unit Database; if not from the RNOH then diagnosis will be otherwise confirmed. Bone mineral density (BMD) will be confirmed with DXA. Where possible measurements will be acquired prior to the start of treatment and then up to 4 follow up visits at flexible time points to allow scheduling to coincide with hospital appointments. Minimum time between vistis should be 2 months.

    Device: spatially offset Raman spectrometer (SORS)

  • Cohort 6: Patients with rickets and osteomalacia

    10-15 participants with rickets and 10-15 participants with osteomalacia. Patients must have been clinically diagnosed with rickets/osteomalacia. Blood tests for 25-hydroxyvitamin D should be less than or equal to 25 nmol/L. Once participants are on treatment further measurements will be made 6 months afterwards. Participants for rickets and osteomalacia groups will be recruited to give a total of 10 complete sets of data per group.

    Device: spatially offset Raman spectrometer (SORS)

  • Cohort 7: 5 patients with suspected bone infection.

    Participants will have been diagnosed at RNOH with a suspected bone infection. Participants will be scanned around the localised area of suspected infection. Participants may have 1 or 2 vists; the latter to take place after all infection has cleared up. This is not subject to a fixed time frame.

    Device: spatially offset Raman spectrometer (SORS)

Interventions

  • Devicespatially offset Raman spectrometer (SORS)

    Raman spectra will be collected non-invasively from patients using a lower power 830 nm laser. A probe is brought into gentle contact with the patients skin and measurements taken. The laser power has a pre-defined safe threshold of 30 mW into a 3.5 mm diameter aperture. Built in device safety features prevent this threshold from being exceeded. The probe that comes into patient contact is suitable for disinfecting.

05

What researchers measure

Primary outcomes

  1. SORS Raman spectral fingerprint for bone disease types and changes over time

    Individual patient data will be pre-processed and extracted after patient participation visits. As cohorts are filled multivariate classification models will be built to validate disease discrimination and validation of the SORS technique.

    Time frame: SORS Raman spectral features will be evaluated using a variety of multi-variate analytical tools e.g. BTEM at time zero and a repeat measure within a year.

06

Study locations

No study locations are listed for this record.

07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT02814591
Lead sponsor
University College, London
Collaborators
Royal National Orthopaedic Hospital NHS Trust, Science & Technology Facilities Council
Responsible party
Sponsor
First posted
Jun 28, 2016
Start date
Oct 2011
Primary completion
Jun 2024 (estimated)
Completion
Jun 2025 (estimated)
Last update
Nov 23, 2022

Study contacts

Helen Birch, Professor
principal investigator · UCL
Panos Gikas, Consultant Rheumatologist
principal investigator · Royal National Orthopaedic Hospital NHS Trust (RNOH)

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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